Restoration of visual function in retinal degeneration mice by ectopic expression of melanopsin

Proc Natl Acad Sci U S A. 2008 Oct 14;105(41):16009-14. doi: 10.1073/pnas.0806114105. Epub 2008 Oct 3.


The rod and cone cells of the mammalian retina are the principal photoreceptors for image-forming vision. They transmit information by means of a chain of intermediate cells to the retinal ganglion cells, which in turn send signals from the retina to the brain. Loss of photoreceptor cells, as happens in a number of human diseases, leads to irreversible blindness. In a mouse model (rd/rd) of photoreceptor degeneration, we used a viral vector to express in a large number of retinal ganglion cells the light sensitive protein melanopsin, normally present in only a specialized subset of the cells. Whole-cell patch-clamp recording showed photoresponses in these cells even after degeneration of the photoreceptors and additional pharmacological or Cd(2+) block of synaptic function. Interestingly, similar responses were observed across a wide variety of diverse types of ganglion cell of the retina. The newly melanopsin-expressing ganglion cells provided an enhancement of visual function in rd/rd mice: the pupillary light reflex (PLR) returned almost to normal; the mice showed behavioral avoidance of light in an open-field test, and they could discriminate a light stimulus from a dark one in a two-choice visual discrimination alley. Recovery of the PLR was stable for at least 11 months. It has recently been shown that ectopic retinal expression of a light sensitive bacterial protein, channelrhodopsin-2, can restore neuronal responsiveness and simple visual abilities in rd/rd mice. For therapy in human photodegenerations, channelrhodopsin-2 and melanopsin have different advantages and disadvantages; both proteins (or modifications of them) should be candidates.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Light
  • Mice
  • Photic Stimulation
  • Photoreceptor Cells, Vertebrate
  • Retinal Degeneration / therapy*
  • Retinal Ganglion Cells / metabolism
  • Rod Opsins / administration & dosage
  • Rod Opsins / genetics*
  • Rod Opsins / therapeutic use
  • Transduction, Genetic*
  • Vision, Ocular / genetics*


  • Rod Opsins
  • melanopsin